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In theory, there is no good reason anyone’s body should activate the immune system to fight against natural things like pollen, dust and healthy foods. But, as anyone with allergies knows, it happens. Finding out how and why is the basis of Mark Kaplan’s research at the Herman B Wells Center for Pediatric Research.
Answering those questions has more potential than merely relieving the suffering that comes with a bad case of hay fever. It may help Kaplan and other researchers learn how to treat a host of autoimmune diseases like multiple sclerosis, Type 1 diabetes and rheumatoid arthritis.
“At the core of most of these diseases is the body’s immune system, which protects us from bacteria and viruses,” says Kaplan. “The problem comes when the body incorrectly identifies something like your joints as an intruder and tries to attack it.” This faulty response is the cause of most chronic inflammatory disease and allergies.
As someone who has suffered from allergies since he was a child, Kaplan has been interested in allergy and immunology research for as long as he can remember. He joined the faculty at the Indiana University School of Medicine in 1998 and the Wells Center in 2005 after completing an undergraduate degree in biology, a doctorate in immunology and microbiology, and two post-doctoral fellowships.
One of the most exciting areas of discovery now on Kaplan’s plate is the study of certain T-cells to learn how they function normally and why they go wrong in diseases like asthma. Even if you aren’t a scientist, you may have heard of T-cells in connection with HIV. A low T-cell count weakens the immune system, making HIV patients vulnerable to serious illnesses.
The body has several kinds of T-cells, which can be divided into subsets. Each group regulates a slightly different type of inflammation. Kaplan and his colleagues study a specific group that hasn’t been well characterized until now, noticing how they interact with other immune cells in the body.
“What we’re learning is that this new subset of T-cells seem to be required to achieve a hypersensitive response in certain organs such as the lungs,” he says. A hypersensitive response is the immediate and sometimes severe reaction people have when they encounter any allergen—whether it’s peanuts or pollen.
Kaplan’s work is linked to a new realm of healthcare known as “personalized medicine,” a term that’s become relevant to all kinds of health conditions, from autoimmune diseases to cancer.
The idea is to confront disease with a targeted one-two punch. “We are using basic science to find certain biomarkers, which are very useful in trying to diagnose patients and identify the best way to treat them,” Kaplan says.
Like many other diseases, asthma isn’t one disease; it’s a broad spectrum of diseases that vary from one patient to the next. One patient’s asthma may trigger inflammation that is controlled by a completely different subset of T-cells than the next patient’s. This is why some people benefit from a certain drug, while others don’t.
As scientists learn how to spot individual biomarkers, they can identify targeted therapies that work for the exact type of disease each person has. After decades of clinical study, this type of research makes it possible for some cancer patients to forgo chemotherapy in favor of biologic drugs that either target their tumors or activate their immune system to fight cancer.
Kaplan and other researchers like him hope to do the same thing for asthma and other diseases. “If we determine that one molecule is really critical for the asthmatic allergic response, we can begin to develop antibodies that would block that protein and treat the disease,” he says. “That’s what we’re ultimately going for.”
These kinds of discoveries could eventually bring better drugs to children who have asthma—a condition that affects one out of 10 children. More to the point, it could keep us from wasting time and money on treatments that don’t work. “We think of cancer as a horrible disease, and it certainly is, but asthma affects a far greater number of kids than cancer, and for about 10 percent of kids, those reactions can be severe and life-threatening,” he says.
The road between basic science and treatment for children can be long, but Kaplan seems unfazed by the distance. He could spend a lifetime analyzing samples and sorting data to look for clues that resolve asthma, allergies and autoimmune diseases. The answers may be just around the corner—or not.
“Even though we may not get to the therapy that will treat a certain disease, we always have the sense that we are on the road to something that could be very valuable later on,” he says. No matter how intriguing their discoveries are, Kaplan and his colleagues at the Wells Center accept the fact that other people—namely those who control grants to fund research—will decide whether their ideas are interesting enough to pursue.